Quintuple Method for Treatment of Multiple Refractory Colorectal Liver Metastases

Sponsor

Liaoning Tumor Hospital & Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05774964

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to explore the therapeutic effect of Quintuple method in the treatment of patients with multiple and refractory liver metastases from colorectal cancer. A randomized single-arm clinical trial was conducted.The intervention group was treated with single SOX chemotherapy, SOX chemotherapy combined with cetuximab targeted therapy, SOX chemotherapy combined with low-dose cetuximab targeted therapy combined with three-drug regimen（Quintuple method）, and the RECIST 1.1 solid tumor evaluation criteria were used to assess the disease.

Condition or Disease	Intervention/Treatment	Phase
For Patients With Colorectal Cancer Liver Metastases Who Were Not Able to Curative Surgical Resection.Focused on the Treatment Effect With the Quintuple Method	Drug: Oxaliplatin Drug: S1 Drug: Cetuximab Drug: Metronidazole Drug: Vitamin A Drug: Folic acid	Phase 2

Detailed Description

Patients with inoperable colorectal liver metastases were selected for genetic testing and enrolled if Kras/Nras/Braf wild-type was detected. The enrolled patients were randomly divided into three groups, in which patients in the single chemotherapy group were treated with SOX regimen alone for chemotherapy;patients in the chemotherapy targeted group were treated with SOX regimen chemotherapy combined with cetuximab targeted therapy; patients in the Quintuple method group were treated with SOX regimen chemotherapy,cetuximab targeted therapy and folic acid, vitamin A, and metronidazole three-drug regimen. Specific drugs were administered at the following doses: SOX regimen every 3 weeks, oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and S1 orally on d2-d15 at 20 mg three times daily. Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks, and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area. Metronidazole 0.4 g/time, qd; vitamin A 5,000 units/time, qd; folic acid 5 mg/time, qd. The latter three drugs were continued until the end of all chemotherapy cycles.Tumor markers associated with liver metastases from colorectal cancer,including magnetic resonance imaging and computed tomography, wererepeated every 3 months and disease was assessed using RECIST 1.1 criteria for the evaluation of solid tumors. The primary end point was death, and the secondary end point was disease progression.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Single-arm, Single-center, Phase II Clinical Trial to Evaluate the Efficacy of Quintuple Method for the Treatment of Multiple Refractory Colorectal Liver Metastases

Anticipated Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Mar 15, 2025

Anticipated Study Completion Date :

Mar 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy alone group Patients treated with chemotherapy using SOX regimen alone. SOX regimen every 3 weeks,oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and tegafur orally on d2-d15 at 20 mg three times daily.	Drug: Oxaliplatin Oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area Drug: S1 Orally on d2-d15 at 20 mg three times daily Other Names: Tegafur,Gimeracil and Oteracil Porassium Capsules
Experimental: Chemotherapy targeted group Patients treated with cetuximab targeted therapy in combination with chemotherapy using SOX regimen.SOX regimen every 3 weeks, oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and tegafur orally on d2-d15 at 20 mg three times daily. Cetuximab combined with chemotherapy was administered simultaneously,once every three weeks, and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area.	Drug: Oxaliplatin Oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area Drug: S1 Orally on d2-d15 at 20 mg three times daily Other Names: Tegafur,Gimeracil and Oteracil Porassium Capsules Drug: Cetuximab Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks,and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area.
Experimental: Quintuple method group Patients treated with a combination of SOX regimen, cetuximab, and folic acid, vitamin A, and metronidazole three-drug regimen.SOX regimen every 3 weeks, oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and tegafur orally on d2-d15 at 20 mg three times daily. Cetuximab combined with chemotherapy was administered simultaneously,once every three weeks, and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area. Metronidazole 0.4g/time, qd;vitamin A 5,000 units/time, qd; folic acid 5 mg/time,qd. The latter three drugs were continued until the end of all chemotherapy cycles.	Drug: Oxaliplatin Oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area Drug: S1 Orally on d2-d15 at 20 mg three times daily Other Names: Tegafur,Gimeracil and Oteracil Porassium Capsules Drug: Cetuximab Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks,and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area. Drug: Metronidazole Metronidazole 0.4g/time, qd Drug: Vitamin A Vitamin A 5,000 units/time, qd Drug: Folic acid Folic acid 5 mg/time, qd

Arm

Intervention/Treatment

Experimental: Chemotherapy alone group

Patients treated with chemotherapy using SOX regimen alone. SOX regimen every 3 weeks,oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and tegafur orally on d2-d15 at 20 mg three times daily.

Drug: Oxaliplatin

Oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area

Drug: S1

Orally on d2-d15 at 20 mg three times daily

Other Names:

Tegafur,Gimeracil and Oteracil Porassium Capsules

Experimental: Chemotherapy targeted group

Patients treated with cetuximab targeted therapy in combination with chemotherapy using SOX regimen.SOX regimen every 3 weeks, oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and tegafur orally on d2-d15 at 20 mg three times daily. Cetuximab combined with chemotherapy was administered simultaneously,once every three weeks, and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area.

Drug: Oxaliplatin

Oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area

Drug: S1

Orally on d2-d15 at 20 mg three times daily

Other Names:

Tegafur,Gimeracil and Oteracil Porassium Capsules

Drug: Cetuximab

Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks,and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area.

Experimental: Quintuple method group

Patients treated with a combination of SOX regimen, cetuximab, and folic acid, vitamin A, and metronidazole three-drug regimen.SOX regimen every 3 weeks, oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area, and tegafur orally on d2-d15 at 20 mg three times daily. Cetuximab combined with chemotherapy was administered simultaneously,once every three weeks, and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area. Metronidazole 0.4g/time, qd;vitamin A 5,000 units/time, qd; folic acid 5 mg/time,qd. The latter three drugs were continued until the end of all chemotherapy cycles.

Drug: Oxaliplatin

Oxaliplatin via intravenous drip on d1 at a dose of 130 mg/m2 × patient 's body surface area

Drug: S1

Orally on d2-d15 at 20 mg three times daily

Other Names:

Tegafur,Gimeracil and Oteracil Porassium Capsules

Drug: Cetuximab

Cetuximab combined with chemotherapy was administered simultaneously, once every three weeks,and intravenous drip was performed before oxaliplatin at a dose of 250 mg/m2 × body surface area.

Drug: Metronidazole

Metronidazole 0.4g/time, qd

Drug: Vitamin A

Vitamin A 5,000 units/time, qd

Drug: Folic acid

Folic acid 5 mg/time, qd

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [Up to approximately 2 years]
Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1
Overall Survival (OS) [Up to approximately 2 years]
OS is the time interval from the start of treatment to death due to any reason or lost of follow-up. For subjects who survived or were lost to follow-up by the data analysis cutoff date, survival was truncated by the subject's last known survival time
Progression Free Survival (PFS) [Up to approximately 2 years]
PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 18-80 years at the time of signing the informed consent form;
Patients with histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV);
Patients with liver metastases found by imaging examination, and liver metastases cannot be radically resected, Or relapse liver metastasis;
At least one measurable metastatic lesion as defined by RECIST version 1.1;
Genetic test results are Kras/Nras/Braf wild-type or mutation type;
ECOG performance status 0-1;
Except for the liver, other organs function well;
Willingness and ability to comply with scheduled visits, treatment plans,laboratory tests, and other study procedures.

Exclusion Criteria:

Patients with non-primary intestinal cancer;
Patients whose primary tumor as well as metastases can be radically resected by surgery;
One or several serious allergies to each drug required for the trial;
Combined with respiratory, circulatory, urinary, hematopoietic and other serious underlying diseases.